Multimodal Cross-Device and Marker-Free Co-Registration of Preclinical Imaging Modalities.

Integrated preclinical multimodal imaging systems, such as X-ray computed tomography (CT) combined with positron emission tomography (PET) or magnetic resonance imaging (MRI) combined with PET, are widely available and typically provide robustly co-registered volumes. However, separate devices are often needed to combine a standalone MRI with an existing PET-CT or to incorporate additional data from optical tomography or high-resolution X-ray microtomography. This necessitates image co-registration, which involves complex aspects such as multimodal mouse bed design, fiducial marker inclusion, image reconstruction, and software-based image fusion. Fiducial markers often pose problems for in vivo data due to dynamic range issues, limitations on the imaging field of view, difficulties in marker placement, or marker signal loss over time (e.g., from drying or decay). These challenges must be understood and addressed by each research group requiring image co-registration, resulting in repeated efforts, as the relevant details are rarely described in existing publications. This protocol outlines a general workflow that overcomes these issues. Although a differential transformation is initially created using fiducial markers or visual structures, such markers are not required in production scans. The requirements for the volume data and the metadata generated by the reconstruction software are detailed. The discussion covers achieving and verifying requirements separately for each modality. A phantom-based approach is described to generate a differential transformation between the coordinate systems of two imaging modalities. This method showcases how to co-register production scans without fiducial markers. Each step is illustrated using available software, with recommendations for commercially available phantoms. The feasibility of this approach with different combinations of imaging modalities installed at various sites is showcased.

Intraperitoneal injections as an alternative method for micro-CT contrast enhanced detection of murine liver tumors.

Micro-computed tomography (micro-CT) coupled with tissue, or vascular, specific contrast agent has emerged as a powerful tool for detecting and monitoring tumor growth in the liver of murine animals. Intravenous injections of contrast agents can be technically challenging and lead to errors that can considerably influence the outcome of a preclinical study, prompting an alternative method. Here we assessed the effectiveness of intraperitoneal injections of polyiodinated triglycerides emulsions (Fenestra LC) in micro-CT imaging of young SCID (8 weeks) and old BALB/c (48 weeks) mice with xenograft or carcinogen-induced liver tumors, respectively, and determined an optimal acquisition time. Utilizing an intraperitoneal injection is a viable alternative administration route for using Fenestra in detection and quantification of murine liver tumor burden.